Antidepressants: A Clinical Update for Medical Practitioners
1984; Elsevier BV; Volume: 59; Issue: 5 Linguagem: Inglês
10.1016/s0025-6196(12)61429-3
ISSN1942-5546
AutoresJarrett W. Richardson, Elliott Richelson,
Tópico(s)Schizophrenia research and treatment
ResumoKnowledge of the pharmacologic actions of antidepressants enables the physician to develop an appropriate rationale for the use of these medications in the medical setting. The appropriate choice of drug and adequate dose, duration, maintenance, termination, therapy, and alternatives should be considered. Knowledge of the pharmacologic actions of antidepressants enables the physician to develop an appropriate rationale for the use of these medications in the medical setting. The appropriate choice of drug and adequate dose, duration, maintenance, termination, therapy, and alternatives should be considered. Depression in isolation or accompanying medical disorders is most frequently recognized and treated initially by primary-care physicians. Depression is also the most common psychiatric disorder encountered by primary-care physicians.1Cassem NH Depression.in: Hackett TP Cassem NH Massachusetts General Hospital Handbook of General Hospital Psychiatry. CV Mosby Company, St. Louis1978: 209-225Google Scholar, 2Moffic HS Paykel ES Depression in medical in-patients.Br J Psychiatry. 1975; 126: 346-353Crossref PubMed Scopus (262) Google Scholar, 3Weissman MM Myers JK Affective disorders in a US urban community: the use of research diagnostic criteria in an epidemiological survey.Arch Gen Psychiatry. 1978; 35: 1304-1311Crossref PubMed Scopus (485) Google Scholar Psychiatric consultation is usually reserved for patients whose episodes of depression are resistant to initial treatment or whose illness is so severe as to warrant hospitalization. Because of the frequency with which physicians prescribe antidepressant medications and the growing number of medications available, an appropriate rationale for their use in various medical situations is important. In this article, we outline the current indications for use of antidepressants. Pharmacologic actions and pharmacokinetics are reviewed, and the clinical implications of this information are discussed. Because the indications for and management of monoamine oxidase inhibitors and lithium carbonate in the treatment of depression are more complex and best determined in consultation with a psychiatrist, the use of these drugs is not reviewed here. Antidepressants are indicated for a major depressive episode with melancholia (“with endogenous features”) (as defined by the DSM-III, the third edition of the Diagnostic and Statistical Manual of the American Psychiatric Association),4Morris JB Beck AT The efficacy of antidepressant drugs: a review of research (1958 to 1972).Arch Gen Psychiatry. 1974; 30: 667-674Crossref PubMed Scopus (215) Google Scholar, 5Gelenberg AJ The rational use of psychotropic drugs: prescribing antidepressants.Drug Ther. November 1979; 9: 95-112Google Scholar, 6Nelson JC Charney DS Primary affective disorder criteria and the endogenous-reactive distinction.Arch Gen Psychiatry. 1980; 37: 787-793Crossref PubMed Scopus (58) Google Scholar, 7Nelson JC Charney DS The symptoms of major depressive illness.Am J Psychiatry. 1981; 138: 1-13Crossref PubMed Scopus (51) Google Scholar for the prevention of recurrent episodes of depression,8Gelenberg AJ Klerman GL Maintenance drug therapy in long-term treatment of depression.in: Brady JP Brodie HKH Controversy in Psychiatry. WB Saunders Company, Philadelphia1978: 279-301Google Scholar and for certain panic-anxiety disorders.9Sheehan DV Ballenger J Jacobsen G Treatment of endogenous anxiety with phobic, hysterical, and hypochondriacal symptoms.Arch Gen Psychiatry. 1980; 37: 51-59Crossref PubMed Scopus (592) Google Scholar, 10Zitrin CM Klein DF Woerner MG Treatment of agoraphobia with group exposure in vivo and imipramine.Arch Gen Psychiatry. 1980; 37: 63-72Crossref PubMed Scopus (235) Google Scholar Other conditions in which these medications are used but have less firmly established efficacy are depressive episodes without melancholic symptoms, compulsive disorders,11Insel TR Murphy DL The psychopharmacological treatment of obsessive-compulsive disorder: a review.J Clin Psychopharmacol. 1981; 1: 304-311Crossref PubMed Scopus (60) Google Scholar hysteroid dysphoria,12Liebowitz MR Klein DF Hysteroid dysphoria.Psychiatr Clin North Am. 1979; 2: 555-575Google Scholar migraine headaches,13Couch JR Hassanein RS Amitriptyline in migraine prophylaxis.Arch Neurol. 1979; 36: 695-699Crossref PubMed Scopus (234) Google Scholar narcolepsy,14Schmidt HS Clark RW Hyman PR Protriptyline: an effective agent in the treatment of the narcolepsy-cataplexy syndrome and hypersomnia.Am J Psychiatry. 1977; 134: 183-185Crossref PubMed Scopus (51) Google Scholar, 15Regestein QR Reich P Mufson MJ Narcolepsy: an initial clinical approach.J Clin Psychiatry. 1983; 44: 166-172PubMed Google Scholar and chronic pain syndromes.16Davis JL Lewis SB Gerich JE Kaplan RA Schultz TA Wallin JD Peripheral diabetic neuropathy treated with amitriptyline and fluphenazine.JAMA. 1977; 238: 2291-2292Crossref PubMed Scopus (111) Google Scholar, 17Tofanetti O Albiero L Galatulas I Genovese E Enhancement of propoxyphene-induced analgesia by doxepin.Psychopharma-cology. 1977; 51: 213-215Crossref PubMed Scopus (9) Google Scholar, 18Carasso RL Yehuda S Streifler M Clomipramine and amitriptyline in the treatment of severe pain.Int J Neurosci. 1979; 9: 191-194Crossref PubMed Scopus (66) Google Scholar, 19Lee R Spencer PSJ Antidepressants and pain: a review of the pharmacological data supporting the use of certain tricyclics in chronic pain.J Int Med Res 5 Suppl. 1977; 1: 146-156Google Scholar They occasionally have been used in children for school phobia,20Gittelman-Klein R Klein DF Controlled imipramine treatment of school phobia.Arch Gen Psychiatry. 1971; 25: 204-207Crossref Scopus (171) Google Scholar enuresis,21Shaffer D Costello AJ Hill ID Control of enuresis with imipramine.Arch Dis Child. 1968; 43: 665-671Crossref PubMed Scopus (50) Google Scholar and hyperactivity syndromes,22Rapoport JL Quinn PO Bradbard G Riddle D Brooks E Imipramine and methylphenidate treatments of hyperactive boys: a double-blind comparison.Arch Gen Psychiatry. 1974; 30: 789-793Crossref PubMed Scopus (157) Google Scholar but these uses are not uniformly accepted practices. Monoamine oxidase inhibitors are indicated for major depression, panic-anxiety disorders, hysteroid dysphoria, and some chronic episodes of depression.23Sheehan DV Claycomb JB Kouretas N Monoamine oxidase inhibitors: prescription and patient management.Int J Psychiatry Med. 1980-1981; 10: 99-121Crossref PubMed Google Scholar In patients without major medical illnesses, the following factors indicate an increased probability of symptom response to antidepressant treatment: (1) severe anhedonia and lack of reactivity of mood to usually pleasurable stimuli, (2) sleep disturbance (particularly middle and terminal insomnia), (3) diurnal variation of symptoms (morning being worse than evening), (4) marked psychomotor retardation or agitation, (5) excessive or inappropriate guilt, and (6) severe anorexia or weight loss.4Morris JB Beck AT The efficacy of antidepressant drugs: a review of research (1958 to 1972).Arch Gen Psychiatry. 1974; 30: 667-674Crossref PubMed Scopus (215) Google Scholar, 5Gelenberg AJ The rational use of psychotropic drugs: prescribing antidepressants.Drug Ther. November 1979; 9: 95-112Google Scholar, 6Nelson JC Charney DS Primary affective disorder criteria and the endogenous-reactive distinction.Arch Gen Psychiatry. 1980; 37: 787-793Crossref PubMed Scopus (58) Google Scholar, 7Nelson JC Charney DS The symptoms of major depressive illness.Am J Psychiatry. 1981; 138: 1-13Crossref PubMed Scopus (51) Google Scholar A history of past success with antidepressant treatment in a patient also suggests an increased probability of symptom response.4Morris JB Beck AT The efficacy of antidepressant drugs: a review of research (1958 to 1972).Arch Gen Psychiatry. 1974; 30: 667-674Crossref PubMed Scopus (215) Google Scholar, 8Gelenberg AJ Klerman GL Maintenance drug therapy in long-term treatment of depression.in: Brady JP Brodie HKH Controversy in Psychiatry. WB Saunders Company, Philadelphia1978: 279-301Google Scholar Recent studies of the diagnosis of depression in patients with major medical illnesses24Plumb MM Holland J Comparative studies of psychological function in patients with advanced cancer—I: self-reported depressive symptoms.Psychosomatic Med. 1977; 39: 264-276PubMed Google Scholar, 25Cavanaugh SA The prevalence of emotional and cognitive dysfunction in a general medical population: using the MMSE, GHQ, and BDI.Gen Hosp Psychiatry. 1983; 5: 15-24Abstract Full Text PDF PubMed Scopus (150) Google Scholar have led to the suggestion that cognitive and affective depressive symptoms, such as are found in the first 14 items of the Beck Depression Inventory (a self-administered depression rating scale),26Beck AT Ward CH Mendelson M Mock J Erbaugh J An inventory for measuring depression.Arch Gen Psychiatry. 1961; 4: 561-571Crossref PubMed Scopus (28335) Google Scholar are more reliable indicators of moderate to severe depression in medically ill patients than are the vegetative signs and symptoms that are usually considered to be indications for drug treatment in psychiatric patients. A Beck Depression Inventory score of 21 or more is a sensitive screen for moderately severe depression in hospitalized medical patients. Unfortunately, no published studies have described a relationship between depression defined in this manner and response to antidepressant medication. We think that vegetative symptoms and signs not explained by the primary medical illness are appropriate indications for antidepressant treatment. Biologic markers and laboratory information that may be helpful in predicting response in the patient without a major medical illness include the following: (1) non-suppression (cortisol value of more than 5 μg/dl in the 24 hours after oral administration of 1 mg of dexamethasone) with the dexamethasone suppression test,27Carroll BJ Use of the dexamethasone suppression test in depression.J Clin Psychiatry 43 Sec. November 1982; 2: 44-48Google Scholar, 28Greden JF Gardner R King D Grunhaus L Carroll BJ Kronfol Z Dexamethasone suppression tests in antidepressant treatment of melancholia: the process of normalization and test-retest reproducibility.Arch Gen Psychiatry. 1983; 40: 493-500Crossref PubMed Scopus (256) Google Scholar (2) change in sleep patterns with antidepressant therapy,29Kupfer D Interaction of EEG sleep, antidepressants, and affective disease.J Clin Psychiatry 43 Sec. November 1982; 2: 30-35Google Scholar (3) transient resolution of behavioral symptoms with a test dose of a stimulant,30Van Kammen DP Murphy DL Prediction of imipramine antidepressant response by a one-day d-amphetamine trial.Am J Psychiatry. 1978; 135: 1179-1184PubMed Google Scholar, 31Sabelli HC Fawcett J Javaid JI Bagri S The methylphenidate test for differentiating desipramine-responsive from nortriptyline-responsive depression.Am J Psychiatry. 1983; 140: 212-214PubMed Google Scholar and (4) adequate therapeutic dosage of antidepressants which leads to appropriate blood levels of the drug.32Friedel RO The relationship of therapeutic response to antidepressant plasma levels: an update.J Clin Psychiatry 43 Sec. November 1982; 2: 37-42Google Scholar For most of these tests, further research is necessary to determine their clinical usefulness. In the meantime, they are best interpreted and integrated into a treatment plan by a psychiatrist with experience in psychopharmacology. Pharmacokinetic studies indicate wide interindividual variation in the absorption, distribution, and excretion of the antidepressants.33Gelenberg AJ Klerman GL Preclinical pharmacology of antidepressants.in: Clark WG del Giudice J Principles of Psychopharmacology. Part 2: Tricyclics. Second edition. Academic Press, New York1978: 317-323Google Scholar, 34Klerman GL Cole JO Clinical pharmacology of imipramine and related antidepressant compounds.Pharmacol Rev. 1965; 17: 101-141PubMed Google Scholar In addition, drug clearance generally declines with aging.35Nies A Robinson DS Friedman MJ Green R Cooper TB Ravaris CL Ives JO Relationship between age and tricyclic antidepressant plasma levels.Am J Psychiatry. 1977; 134: 790-793PubMed Google Scholar Table 1 outlines the recommended daily doses and projected optimal therapeutic plasma ranges of tricyclic and other antidepressants. Of particular note is the substantiated 10- to 30-fold variation in individual metabolism, which necessitates specific attention to individualization of drug dosage and emphasizes the frequent need to monitor drug plasma levels to achieve an appropriate therapeutic response. The concept of a therapeutic window (that is, a blood level range below and above which the drug is ineffective) has been thoroughly evaluated only for nortriptyline.36Asberg M Plasma nortriptyline levels—relationship to clinical effects.Clin Pharmacol Ther. 1974; 16: 215-229PubMed Google Scholar The other drugs for which plasma assays are available generally have a recommended minimal therapeutic plasma level.37Risch SC Huey LY Janowsky DS Plasma levels of tricyclic antidepressants and clinical efficacy: review of the literature.J Clin Psychiatry. 1979; 40 (58-69): 4-16Google Scholar Protriptyline and nortriptyline, in comparison with other antidepressants, demonstrate increased potency; therefore, a smaller mean daily dose of these drugs should be prescribed. A single daily dose is appropriate for most of these drugs.38Weise CC Stein MK Pereira-Ogan J Csanalosi I Rickels K Amitriptyline once daily vs three times daily in depressed outpatients.Arch Gen Psychiatry. 1980; 37: 555-560Crossref PubMed Scopus (12) Google ScholarTable 1Pharmacokinetics, Daily Doses, and Projected Therapeutic Plasma Ranges of Tricyclic and Other AntidepressantsT½ (h)Drug (generic and trade names)Individual variation in metabolismMeanRangeStarting dosage*For any of the listed antidepressants, elderly persons should be treated with about half of the recommended dosage for adults. (mg/day)Recommended daily dose for adults*For any of the listed antidepressants, elderly persons should be treated with about half of the recommended dosage for adults. (mg)Dosage range (mg/day)Projected optimal therapeutic plasma range (ng/ml)Tricyclic: tertiary amines Amitriptyline (Elavil, Endep)10-fold1610–2550150–20050–300125–250 Trimipramine (Surmontil)………50150–20050–300… Doxepin (Adapin, Sinequan)10- to 15-fold178–2450150–25050–30075–200 Imipramine (Janimine, SK-Pramine, Tofranil)30-fold2818–3450150–20050–300150–300Tricyclic: secondary amines Protriptyline (Vivactil)10- to 15-fold7855–1271030–4015–6050–150 Nortriptyline (Aventyl, Pamelor)30-fold2716–362575–10030–10050–150 Desipramine (Norpramin, Pertofrane)10-fold2112–3050150–25050–300150–300Dibenzoxazepine Amoxapine (Asendin)……8–30†Amoxapine, 8 hours; 8-hydroxyamoxapine, 30 hours.150150–20050–300160–800‡Of total drug measured, amoxapine = 10-20% and 8-hydroxyamoxapine = 80-90%.Tetracyclic Maprotiline (Ludiomil)…47…50150–20050–300200–300Triazolopyridine Trazodone (Desyrel)…43–650–150150–40050–600…* For any of the listed antidepressants, elderly persons should be treated with about half of the recommended dosage for adults.† Amoxapine, 8 hours; 8-hydroxyamoxapine, 30 hours.‡ Of total drug measured, amoxapine = 10-20% and 8-hydroxyamoxapine = 80-90%. Open table in a new tab Other pharmacokinetic information of clinical importance39Baldessarini RJ Overview of recent advances in antidepressant pharmacology.McLean Hosp J. April 1981; Google Scholar is that these agents are highly lipid soluble and therefore have a high volume of distribution. They are also strongly bound to plasma proteins. The elimination half-lives of most of the antidepressants in Table 1 are in the 16- to 28-hour range. The half-lives of maprotiline and protriptyline, however, are much longer; consequently, use of these drugs results in not only the requirement of a longer time to achieve a steady state after initiation of treatment but also the need for a longer period of observation for complications after ingestion of an overdose. The pharmacologic features of the antidepressants in use in the United States have been thoroughly reviewed recently by one of us.40Richelson E Pharmacology of antidepressants in use in the United States.J Clin Psychiatry 43 Sec. November 1982; 2: 4-11Google Scholar The blockade of certain neurotransmitter receptors by antidepressants (Table 2) is responsible for numerous side effects of treatment (Table 3). The antidepressants that have been available and in standard use for some time in the United States are similar in their α2-adrenergic receptor affinities but have a wide range of histamine H1,45Richelson E Tricyclic antidepressants and histamine H1 receptors.Mayo Clin Proc. 1979; 54: 669-674PubMed Google Scholar histamine H2,42Kanba S Richelson E Antidepressants are weak competitive antagonists of histamine H2 receptors in dissociated tissue from the guinea pig hippocampus.Eur J Pharmacol. 1983; 94: 313-318Crossref PubMed Scopus (25) Google Scholar muscarinic,43 α1-adrenergic, and serotonergic affinities. The side effects of greatest importance for drug selection in a medical situation are the anticholinergic (antimuscarinic) and antihistaminic (H1) effects. In general, the tertiary amines are associated with major antihistaminic and anticholinergic side effects, and the secondary amines, particularly desipramine, cause less severe antihistaminic and anticholinergic side effects.Table 2Antidepressant Affinities*107 × 1/KD, in which KD = equilibrium dissociation constant in molarity. for Some Neurotransmitter ReceptorsHistamineα-AdrenergicDrug (generic and trade names)H1†Data for human brain from Richelson E, Nelson A.41H2‡Data from Kanba S, Richelson E.42Muscarinic§Data from El-Fakahany E, Richelson E.43α1†Data for human brain from Richelson E, Nelson A.41α2‡Data from Kanba S, Richelson E.42SerotoninData from Tang SW, Seeman P.44Tricyclic: tertiary amines Doxepin (Adapin, Sinequan)4200.0711.34.20.0910.52 Trimipramine (Surmontil)3700.0421.74.20.1500.38 Amitriptyline (Elavil, Endep)910.0535.53.70.1100.52 Imipramine (Janimine, SK-Pramine, Tofranil)9.10.0301.11.10.0310.12Tricyclic: secondary amines Nortriptyline (Aventyl, Pamelor)100.00620.671.60.0400.33 Protriptyline (Vivactil)4.00.0274.00.750.0150.11 Desipramine (Norpramin, Pertofrane)0.910.0080.500.750.0140.04Dibenzoxazepine Amoxapine (Asendin)4.00.0120.102.00.038…Tetracyclic Maprotiline (Ludiomil)500.0220.171.10.0110.55Triazolopyridine Trazodone (Desyrel)0.290.00670.000312.80.200…* 107 × 1/KD, in which KD = equilibrium dissociation constant in molarity.† Data for human brain from Richelson E, Nelson A.41Richelson E, Nelson A: Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro (submitted for publication)Google Scholar‡ Data from Kanba S, Richelson E.42Kanba S Richelson E Antidepressants are weak competitive antagonists of histamine H2 receptors in dissociated tissue from the guinea pig hippocampus.Eur J Pharmacol. 1983; 94: 313-318Crossref PubMed Scopus (25) Google Scholar§ Data from El-Fakahany E, Richelson E.43El-Fakahany E Richelson E Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain.Br J Pharmacol. 1983; 78: 97-102PubMed Google Scholar// Data from Tang SW, Seeman P.44Tang SW Seeman P Effect of antidepressant drugs on serotoninergic and adrenergic receptors.Naunyn Schmiedebergs Arch Pharmacol. 1980; 311: 255-261Crossref PubMed Scopus (119) Google Scholar Open table in a new tab Table 3Side Effects of Antidepressants Due to Receptor BlockadeAntihistamineAntimuscarinicH1H2Anti-α1-adrenergic Blurred visionAttack or exacerbation of narrow-angle glaucomaDry mouthConstipationUrinary retentionMemory dysfunctionSpeech blockageDecreased sweating SedationDrowsinessHypotension (?)Weight gain (?)Mental confusion (?) Postural hypotension, dizzinessReflex tachycardia Open table in a new tab Published reports have also described rare hematologic (agranulocytosis)46Ebert MH Shader RI Hematological effects.in: Shader RI DiMascio A Psychotropic Drug Side Effects: Clinical and Theoretical Perspectives. Williams & Wilkins Company, Baltimore1970: 164-174Google Scholar and hepatic (cholestasis)47Morgan MH Read AE Antidepressants and liver disease.Gut. 1972; 13: 697-701Crossref PubMed Scopus (18) Google Scholar, 48Horst DA Grace ND LeCompte PM Prolonged cholestasis and progressive hepatic fibrosis following imipramine therapy.Gastroenterology. 1980; 79: 550-554PubMed Scopus (44) Google Scholar effects, drug interactions,49Baldessarini RJ Chemotherapy in Psychiatry. Harvard University Press, Cambridge, Massachusetts1977: 109-111Google Scholar and possible teratogenicity,50Rachelefsky GS Flynt Jr, JW Ebbin AJ Wilson MG Possible teratogenicity of tricyclic antidepressants (letter to the editor).Lancet. 1972; 1: 838Abstract PubMed Scopus (12) Google Scholar which should be considerations in prescription and clinical management. Several antidepressant drugs (amoxapine, trimipramine, maprotiline, and trazodone) have been introduced within the last several years. Amoxapine, maprotiline, and trazodone are remarkable primarily for their relatively minor antimuscarinic side effects.40Richelson E Pharmacology of antidepressants in use in the United States.J Clin Psychiatry 43 Sec. November 1982; 2: 4-11Google Scholar Their efficacy and tolerability with regard to associated cardiac and central nervous system side effects are still not clearly established.51Cassem N Cardiovascular effects of antidepressants.J Clin Psychiatry 43 Sec. November 1982; 2: 22-28Google Scholar, 52Janowsky D Curtis G Zisook S Kuhn K Resovsky K Le Winter M Ventricular arrhythmias possibly aggravated by trazodone.Am J Psychiatry. 1983; 140: 796-797Crossref PubMed Scopus (58) Google Scholar, 53Trimble MR New antidepressant drugs and the seizure threshold.Neuropharmacology. 1980; 19: 1227-1228Crossref PubMed Scopus (29) Google Scholar, 54Kim WY Seizures associated with maprotiline (letter to the editor).Am J Psychiatry. 1982; 139: 845-846PubMed Google Scholar, 55Koval G VanNuis C Davis TD Seizures associated with amoxapine (letter to the editor).Am J Psychiatry. 1982; 139: 845PubMed Google Scholar, 56Goldberg MJ Spector R Amoxapine overdose: report of two patients with severe neurologic damage.Ann Intern Med. 1982; 96: 463-464Crossref PubMed Scopus (26) Google Scholar Much of the aforementioned information is derived from in vitro studies, and individual patient variability is considerable in terms of side effects and symptom response. Nevertheless, a general set of guidelines for choosing a drug in various clinical situations can be constructed on the basis of the foregoing pharmacologic information.57Stern SL Rush AJ Mendels J Toward a rational pharmacotherapy of depression.Am J Psychiatry. 1980; 137: 545-552PubMed Google Scholar All of the antidepressants mentioned are reported to have equivalent clinical efficacy; however, some of them have been available and in clinical use for a long time and therefore have a longer established efficacy. In general, these older drugs are also considerably less expensive. A patient will usually tolerate the side effects if they are carefully explained and monitored through the initial period of treatment. The initial dose is approximately a third of the generally recommended target dose (Table 1). The dose is then adjusted incrementally every third or fourth day, as tolerated, until the target dose is reached. Because individual metabolism varies extensively, particularly in elderly patients, the achievement of adequate, nontoxic dosages may necessitate the checking of the blood level of the drug after a steady state has been reached (usually after five half-lives). For most patients, however, careful clinical supervision and monitoring are adequate. If antimuscarinic side effects (Table 3) become intolerable, use of one of the more expensive, but generally better tolerated, newer antidepressants may be helpful. Knowledge of the pharmacologic features of the antidepressants facilitates the development of a rationale for improved selection of antidepressants in certain clinical situations in which depression coexists with a major medical disorder. Table 4 summarizes the preferred antidepressants in those situations.Table 4Preferred Antidepressants When Specific Medical Disorders Coexist With DepressionI.CardiovascularA.Congestive heart failure or coronary artery disease—maprotilineB.Conduction defect—maprotilineC.Hypertension treated with guanethidine—trimipramine, trazodoneD.Hypertension treated with prazosin—protriptyline, desipramineE.Hypertension treated with clonidine or α-methyldopa—protriptyline, desipramine, maprotilineF.Untreated mild hypertension—imipramineG.Postural hypotension—maprotiline, trazodone (avoid imipramine and amitriptyline)II.NeurologicA.Seizure disorder—monoamine oxidase inhibitor best, secondary amine (desipramine) better than tertiary amine (imipramine) or maprotilineB.Organic brain syndrome—trazodone, amoxapine, maprotiline, desipramineC.Chronic pain syndrome—doxepin, trimipramine, amitriptyline, nortriptylineD.Migraine headaches—doxepin, trimipramine, amitriptyline, nortriptylineE.Psychosis—antidepressant plus neuroleptic, amoxapineF.Parkinsonism—amitriptyline, protriptyline, trimipramine, doxepin, imipramineG.Tardive dyskinesia—trazodone, amoxapine, maprotiline, desipramineIII.Allergic—doxepin, amitriptyline, trimipramine, imipramine, nortriptylineIV.GastrointestinalA.Chronic diarrhea—doxepin, trimipramine, amitriptyline, imipramine, protriptylineB.Chronic constipation—trazodone, amoxapine, maprotiline, desipramineC.Peptic ulcer disease—doxepin, trimipramine, amitriptyline, imipramineV.UrologicA.Neurogenic bladder—trazodone, amoxapine, maprotiline, desipramineB.Organic impotence—trazodone, amoxapine, maprotiline, desipramineVI.Ophthalmologic (glaucoma)—trazodone, amoxapine, maprotiline, desipramine Open table in a new tab Amitriptyline and imipramine produce considerably more tachycardia, postural hypotension, and quinidine-like effects than do maprotiline and trazodone.39Baldessarini RJ Overview of recent advances in antidepressant pharmacology.McLean Hosp J. April 1981; Google Scholar Therefore, in patients with congestive heart disease, ischemic heart disease, or conduction defect, maprotiline and trazodone are the preferred drugs. Even trazodone, however, has recently been reported to have some cardiovascular side effects.51Cassem N Cardiovascular effects of antidepressants.J Clin Psychiatry 43 Sec. November 1982; 2: 22-28Google Scholar, 52Janowsky D Curtis G Zisook S Kuhn K Resovsky K Le Winter M Ventricular arrhythmias possibly aggravated by trazodone.Am J Psychiatry. 1983; 140: 796-797Crossref PubMed Scopus (58) Google Scholar Trimipramine and trazodone inhibit norepinephrine uptake the least and, therefore, are appropriate choices in treating a depressed patient who requires guanethidine.39Baldessarini RJ Overview of recent advances in antidepressant pharmacology.McLean Hosp J. April 1981; Google Scholar Desipramine and protriptyline have the least affinity for α1-adrenergic receptors and should produce the least potentiation of the antihypertensive effects of prazosin.58Charney DS Heninger GR Sternberg DE Redmond DE Leckman JF Maas JW Roth RH Presynaptic adrenergic receptor sensitivity in depression: the effect of long-term desipramine treatment.Arch Gen Psychiatry. 1981; 38: 1334-1340Crossref PubMed Scopus (107) Google Scholar In general, the antidepressant compounds are relatively weak (maprotiline, desipramine, and protriptyline are the weakest) α2-adrenergic receptor antagonists but in some cases can interfere with antihypertensive treatment with clonidine or α-methyldopa.59Van Spanning HW Van Zwieten PA The interference of tricyclic antidepressants with the central hypotensive effect of clonidine.Eur J Pharmacol. 1973; 24: 402-404Crossref PubMed Scopus (42) Google Scholar Imipramine produces orthostatic hypotension more often than do the other antidepressants60Glassman AH Bigger Jr, JT Giardina EV Kantor SJ Perel JM Davies M Clinical characteristics of imipramine-induced orthostatic hypotension.Lancet. 1979; 1: 468-472Abstract PubMed Scopus (135) Google Scholar and in some patients obviates other antihypertensive treatment. In limited studies of patients with heart disease, therapeutic doses of antidepressants produced no appreciable effect on left ventricular ejection fraction or left ventricular wall motion.61Taylor DGE Braithwaite RA Cardiac effects of tricyclic antidepressant medication, a preliminary study of nortriptyline.Swed Heart J. 1978; 40: 1005-1009Crossref Scopus (45) Google Scholar Although no studies have been done on the use of antidepressant drugs in the period immediately after myocardial infarction or coronary artery bypass, imipramine and amitriptyline have been used with efficacy and safety in patients with depression 4 months after severe cardiac injury.62Raskind M Veith R Barnes R Gumbrecht G Cardiovascular and antidepressant effects of imipramine in the treatment of secondary depression in patients with ischemic heart disease.Am J Psychiatry. 1982; 139: 1114-1117PubMed Google Scholar Amoxapine, imipramine, and maprotiline lower the seizure threshold more than do desipramine and monoamine oxidase inhibitors; thus, these last two drugs are preferred in depressed patients with seizure disorders.53Trimble MR New antidepressant drugs and the seizure threshold.Neuropharmacology
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